Why Your Endometriosis Pain Can Feel So Unrelenting

If you live with endometriosis, you’ve probably noticed something that doesn’t make sense on the surface: pain that keeps coming back, bowel or bladder symptoms that feel “tethered,” and flare patterns that don’t always match what your scans show. You might even be told your disease is “mild,” while your day-to-day life feels anything but.

One helpful way to make sense of this is to understand that endometriosis lesions often don’t behave like simple “implants.” They can act more like active wounds that keep trying to heal—creating inflammation, new blood vessels, and scarring (fibrosis). Recent evidence looking across many studies points to a family of signaling proteins (the TGF-β superfamily) as one of the drivers behind that “sticky, scarring, persistent” behavior. This isn’t an immediate new treatment you can start tomorrow, but it can absolutely help you make more informed choices: which symptoms are likely driven by fibrosis, why hormones help some people more than others, and what to ask your clinician when pain persists.

What this means in real life: inflammation + fibrosis can be a pain engine

TGF-β (especially TGF-β1 and TGF-β2) shows up at higher levels in many endometriosis-related places—blood, peritoneal fluid, peritoneal tissues, and lesion tissue—in a lot of studies, though not all results match perfectly. The practical takeaway isn’t “go test your TGF-β.” The takeaway is this:

When endometriosis is actively promoting adhesions, invasion, immune disruption, and fibrosis, you may feel:

• Pain that becomes more constant (not just during periods)
• Deep pain with sex, bowel movements, urination, or certain movements
• A sensation of pulling/tightness—sometimes worsening over time
• Symptoms that don’t correlate well with cyst size or superficial findings

Fibrosis matters because scar-like tissue can produce nerve growth factors which increases the number of microscopic nociceptive (pain sensing) nerve endings, irritate nerves, restrict organ mobility, and maintain inflammation. That can also help explain why some people feel worse over the years—even if lesions aren’t “spreading everywhere.”

So… is there a treatment that “blocks TGF-β” for endometriosis?

Not in routine clinical care right now.

You may see headlines implying that “blocking TGF-β cures endometriosis.” That’s not where the evidence is. The strongest message from this body of research is that these pathways are promising future targets, but they’re not yet established, safe, endometriosis-specific treatments you can ask your doctor to prescribe today. In addition, blocking the nerve sensation is not a "cure" anyway. But it is something that will reduce pain and help people feel better in the future.

That said, understanding these pathways can still help you make better decisions with the tools we do have now—because many current treatments are indirectly aimed at the same downstream results: reducing inflammation, suppressing lesion activity, and limiting progression/recurrence.

Where this connects to your current options (and how to think about them)

Even without a “TGF-β blocker,” you and your doctor are often trying to calm the same processes that TGF-β-related signals appear to amplify, indirectly.

Hormonal suppression (pill, progestins, IUD, GnRH options)

If your symptoms improve on hormonal treatment, that can be a sign that cycling inflammation and bleeding within lesions is a major driver for you. Hormonal suppression can reduce pain for many patients, but it may be less effective when pain is already heavily driven by fibrosis, adhesions, and nerve involvement—because scar tissue doesn’t simply melt away when hormones are suppressed.

Practical implication: if you’ve tried multiple hormonal options and pain remains high, it’s reasonable to discuss whether your symptom pattern suggests deep disease, adhesions, or significant fibrosis, and whether imaging and/or surgical consultation makes sense.

Surgery (especially excision) and the “recurrence” conversation

TGF-β–linked processes include adhesion and invasion behaviors, plus fibrosis. This supports what many patients experience: endometriosis is not just “extra tissue,” it can be biologically active in ways that promote persistence.

Practical implication: when discussing surgery, it’s worth asking not only “Can you remove the lesions?” but also:

• “What is your approach to deep disease, fibrosis and adhesions?”
• “What’s your plan to reduce recurrence risk afterward?”

Post-op hormonal suppression is often suggested for recurrence prevention (when pregnancy isn’t the immediate goal). Your best plan depends on your symptoms, fertility goals, and surgical findings. However, even if the scientific proof is not the greatest, the overall consensus is that in most cases doing something is better than nothing. This can range from compounded bio-identical progesterone, to oral forms of progesterone, to synthetic progestins and so on.

Pain care that treats your nervous system too

When inflammation and fibrosis have been present for years, your nervous system can become sensitized (pain pathways become overprotective). This doesn’t mean pain is “in your head.” It means your body has been living with repeated threat signals.

Practical implication: a complete plan may need more than hormones or surgery alone—think pelvic floor physical therapy, neuropathic pain medications for central nervous system desensitization when appropriate, trauma-informed care, and targeted strategies for flares.

Why results vary so much from person to person

One frustrating theme in endometriosis research is inconsistency. Even within this area, while many studies report higher TGF-β levels in certain compartments, at least one reported lower TGF-β1 expression in ectopic endometrium—suggesting real biological diversity. In other words, the molecular drivers of endometriosis are likely different from person to person. It is not likely one disease that affects everyone the same way, meaning endometriosis is not one uniform disease.

Practical takeaways for your next appointment

Use this as a script to steer the conversation toward what actually improves your quality of life:

• “Do my symptoms sound more consistent with inflammation, deep disease, adhesions, or pelvic floor involvement?”
• “If fibrosis/adhesions are suspected, what imaging is most useful for my situation, and what might it miss?”
• “What’s our timeline to decide if this treatment is working—and what’s the next step if it isn’t?”
• “If I’m considering surgery, what is your experience with excision of deep disease, fibrosis and adhesions? What outcomes should I realistically expect?”
• “What’s our plan for recurrence prevention after surgery (or if I delay surgery) given my fertility goals?”

Reality check: what we still don’t know (and how to protect yourself from hype)

This pathway-based research supports the idea that fibrosis and immune signaling are part of endometriosis progression—but it does not prove that one molecule “causes” endometriosis in humans, nor does it give you a validated diagnostic blood test today.

The most useful way to apply this information is to reframe your care:

• Persistent symptoms may reflect active biology, not personal failure or “low pain tolerance.”
• If a treatment only targets one aspect (like cycling hormones), you still need strategies for fibrosis/adhesions, pelvic floor dysfunction, and nervous system sensitization.
• Promising targets are coming, but right now the best results typically come from individualized, multi-tool care—and from clinicians who take your symptoms seriously even when tests are imperfect.